The major breast/ovarian cancer predisposition genes, BRCA1 and BRCA2, function in double strand break (DSB) repair and sister chromatid recombination (SCR), a potentially error-free pathway of homologous recombination (HR). Some BRCA1 missense mutations (encoding point mutant proteins) are known to be either neutral or pathogenic. However, most missense mutants—termed “variants of uncertain significance” (VUS)—are difficult to classify due to their scarcity in the human population. Therefore, if a woman carries a germ line BRCA1 VUS allele, her cancer risk is unknown. Methods of characterizing the functional significance of such variants are urgently required to distinguish variants that increase the risk of breast cancer from those that are not functionally significant.